This project is concerned with several aspects of investigations of the roles of replication competent murine leukemia viruses (MuLVs) in development of spontaneous or induced neoplastic and non-neoplastic disease in laboratory mice. Several classes of MuLVs are known, categorized on the basis of host range and ability to establish interference to superinfection, and pathogenic, biologic, or molecular variants within each class have been identified. Mice of selected strains are inoculated with various virus preparations, usually biologically cloned ecotropic or recombinant MCF MuLVs. Tests are carried out for replication of input virus and generation of new recombinant viruses, tumors or other lesions are studied histopathologically and when appropriate by surface antigen phenotyping, and may be examined for new proviral integrations, for rearrangements of cellular genes, or for expression of activated gene products. Insights into the molecular basis of pathogenicity and tissue specificity of disease are obtained by construction of recombinant viruses from molecular clones of related viruses with different pathogenic properties. Results of current studies include characterization of helper independent lymphomagenic MCF viruses, and the molecular cloning and partial sequencing of one of these; definition in Moloney (T-cell lymphomagenic) and Friend (erythroleukemia inducing) MuLVs those sequences responsible for disease specificity: the direct repeat region, having the properties of transcriptional enhancers; and recovery of new MuLV from California wild mice, the source of previous isolates with interesting pathogenic properties.